Document Detail

Regulation of Notch signaling during T- and B-cell development by O-fucose glycans.
MedLine Citation:
PMID:  19594638     Owner:  NLM     Status:  MEDLINE    
Notch signaling is required for the development of all T cells and marginal zone (MZ) B cells. Specific roles in T- and B-cell differentiation have been identified for different Notch receptors, the canonical Delta-like (Dll) and Jagged (Jag) Notch ligands, and downstream effectors of Notch signaling. Notch receptors and ligands are post-translationally modified by the addition of glycans to extracellular domain epidermal growth factor-like (EGF) repeats. The O-fucose glycans of Notch cell-autonomously modulate Notch-ligand interactions and the strength of Notch signaling. These glycans are initiated by protein O-fucosyltransferase 1 (Pofut1), and elongated by the transfer of N-acetylglucosamine (GlcNAc) to the fucose by beta1,3GlcNAc-transferases termed lunatic, manic, or radical fringe. This review discusses T- and B-cell development from progenitors deficient in O-fucose glycans. The combined data show that Lfng and Mfng regulate T-cell development by enhancing the interactions of Notch1 in T-cell progenitors with Dll4 on thymic epithelial cells. In the spleen, Lfng and Mfng cooperate to modify Notch2 in MZ B progenitors, enhancing their interaction with Dll1 on endothelial cells and regulating MZ B-cell production. Removal of O-fucose affects Notch signaling in myelopoiesis and lymphopoiesis, and the O-fucose glycan in the Notch1 ligand-binding domain is required for optimal T-cell development.
Pamela Stanley; Cynthia J Guidos
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  230     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-14     Completed Date:  2009-09-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  201-15     Citation Subset:  IM    
Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA.
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MeSH Terms
B-Lymphocytes / immunology*,  metabolism
Cell Differentiation / immunology
Fucose / immunology*,  metabolism
Intercellular Signaling Peptides and Proteins / immunology,  metabolism
Polysaccharides / immunology*,  metabolism
Receptors, Notch / immunology*,  metabolism
Signal Transduction / immunology
T-Lymphocytes / immunology*,  metabolism
Transferases / immunology,  metabolism
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/Polysaccharides; 0/Receptors, Notch; 3713-31-3/Fucose; EC 2.-/Transferases

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